Marker delivery device with releasable plug

ABSTRACT

A marker delivery device includes an elongated delivery cannula which has a distal end section, an inner lumen and a discharge opening in the distal end section in communication with the inner lumen. At least one elongated fibrous marker body is slidably disposed within the inner lumen of the elongated delivery cannula. The at least one elongated fibrous marker body includes a plurality of bioabsorbable polymeric strands. The strands are compressed to a compressed configuration and bound together in the compressed configuration with a polymer binding agent prior to insertion into the elongated delivery cannula. A releasable plug is disposed within a distal portion of the inner lumen and distal to the at least one elongated fibrous marker body so as to at least partially occlude the discharge opening in the distal end section.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 10/753,694 entitled “MARKER DELIVERY DEVICE WITH RELEASABLEPLUG”, filed Jan. 7, 2004, which is a continuation-in-part of U.S.patent application Ser. No. 10/444,770, filed May 23, 2003.

Also, this application is a continuation-in-part of U.S. patentapplication Ser. No. 12/852,286 entitled CAVITY-FILLING BIOPSY SITEMARKERS, filed Aug. 6, 2010, which is a continuation of U.S. patentapplication Ser. No. 10/990,327, filed Nov. 16, 2004, now U.S. Pat. No.7,792,569, which is a continuation of U.S. patent application Ser. No.10/124,757, filed Apr. 16, 2002, now U.S. Pat. No. 6,862,470, which is acontinuation-in-part of U.S. patent application Ser. No. 09/717,909,filed Nov. 20, 2000, now U.S. Pat. No. 6,725,083, which is acontinuation-in-part of U.S. patent application Ser. No. 09/343,975,filed Jun. 30, 1999, now U.S. Pat. No. 6,347,241, which is acontinuation-in-part of U.S. patent application Ser. No. 09/241,936,filed Feb. 2, 1999, now U.S. Pat. No. 6,161,034.

Also, this application is a continuation-in-part of U.S. patentapplication Ser. No. 12/592,020 entitled PLUGGED TIP DELIVERY TUBE FORMARKER PLACEMENT, filed Nov. 18, 2009, which is a continuation of U.S.patent application Ser. No. 10/174,401, filed Jun. 17, 2002, now U.S.Pat. No. 7,651,505.

All the above from which priority is claimed and are incorporated hereinby reference in their entireties.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention is generally directed to devices and methods for thedelivery of remotely detectable markers to a desired location within apatient's body. In particular, the invention is directed to devices andmethods configured to retain a remotely detectable marker within adelivery device before delivery to a desired intracorporeal location.

2. Description of the Related Art

In diagnosing and treating certain medical conditions, it is oftendesirable to mark a suspicious body site for the subsequent taking of abiopsy specimen, for delivery of medicine, radiation, or othertreatment, for the relocation of a site from which a biopsy specimen wastaken, or at which some other procedure was performed. As is known,obtaining a tissue sample by biopsy and the subsequent examination aretypically employed in the diagnosis of cancers and other malignanttumors, or to confirm that a suspected lesion or tumor is not malignant.The information obtained from these diagnostic tests and/or examinationsis frequently used to devise a therapeutic plan for the appropriatesurgical procedure or other course of treatment.

In many instances, the suspicious tissue to be sampled is located in asubcutaneous site, such as inside a human breast. To minimize surgicalintrusion into a patient's body, it is often desirable to insert a smallinstrument, such as a biopsy needle, into the body for extracting thebiopsy specimen while imaging the procedure using fluoroscopy,ultrasonic imaging, x-rays, magnetic resonance imaging (MRI) or anyother suitable form of imaging technique. Examination of tissue samplestaken by biopsy is of particular significance in the diagnosis andtreatment of breast cancer. In the ensuing discussion, the biopsy andtreatment site described will generally be the human breast, althoughthe invention is suitable for marking biopsy sites in other parts of thehuman and other mammalian body as well.

Periodic physical examination of the breasts and mammography areimportant for early detection of potentially cancerous lesions. Inmammography, the breast is compressed between two plates whilespecialized x-ray images are taken. If an abnormal mass in the breast isfound by physical examination or mammography, ultrasound may be used todetermine whether the mass is a solid tumor or a fluid-filled cyst.Solid masses are usually subjected to some type of tissue biopsy todetermine if the mass is cancerous.

If a solid mass or lesion is large enough to be palpable, a tissuespecimen can be removed from the mass by a variety of techniques,including but not limited to open surgical biopsy, a technique known asFine Needle Aspiration Biopsy (FNAB) and instruments characterized as“vacuum assisted large core biopsy devices”.

If a solid mass of the breast is small and non-palpable (e.g., the typetypically discovered through mammography), a vacuum assisted large corebiopsy procedure is usually used. In performing a stereotactic biopsy ofa breast, the patient lies on a special biopsy table with her breastcompressed between the plates of a mammography apparatus and twoseparate x-rays or digital video views are taken from two differentpoints of view. A computer calculates the exact position of the lesionas well as depth of the lesion within the breast. Thereafter, amechanical stereotactic apparatus is programmed with the coordinates anddepth information calculated by the computer, and such apparatus is usedto precisely advance the biopsy needle into the small lesion. Thestereotactic technique may be used to obtain histologic specimens.Usually at least five separate biopsy specimens are obtained fromlocations around the small lesion as well as one from the center of thelesion.

The available treatment options for cancerous lesions of the breastinclude various degrees of mastectomy or lumpectomy, radiation therapy,chemotherapy and combinations of these treatments. However,radiographically visible tissue features, originally observed in amammogram, may be removed, altered or obscured by the biopsy procedure,and may heal or otherwise become altered following the biopsy. In orderfor the surgeon or radiation oncologist to direct surgical or radiationtreatment to the precise location of the breast lesion several days orweeks after the biopsy procedure was performed, it is desirable that abiopsy site marker be placed in the patient's body to serve as alandmark for subsequent location of the lesion site. A biopsy sitemarker may be a permanent marker (e.g., a metal marker visible underx-ray examination), or a temporary marker (e.g., a bioresorbable markerdetectable with ultrasound). While current radiographic type markers maypersist at the biopsy site, an additional mammography generally must beperformed at the time of follow up treatment or surgery in order tolocate the site of the previous surgery or biopsy. In addition, once thesite of the previous procedure is located using mammography, the sitemust usually be marked with a location wire which has a hook on the endwhich is advanced into site of the previous procedure. The hook is meantto fix the tip of the location wire with respect to the site of theprevious procedure so that the patient can then be removed from theconfinement of the mammography apparatus and the follow-up procedureperformed. However, as the patient is removed from the mammographyapparatus, or otherwise transported the position of the location wirecan change or shift in relation to the site of the previous procedure.This, in turn, can result in follow-up treatments being misdirected toan undesired portion of the patient's tissue.

As an alternative or adjunct to radiographic imaging, ultrasonic imaging(herein abbreviated as “USI”) or visualization techniques can be used toimage the tissue of interest at the site of interest during a surgicalor biopsy procedure or follow-up procedure. USI is capable of providingprecise location and imaging of suspicious tissue, surrounding tissueand biopsy instruments within the patient's body during a procedure.Such imaging facilitates accurate and controllable removal or samplingof the suspicious tissue so as to minimize trauma to surrounding healthytissue.

For example, during a breast biopsy procedure, the biopsy device isoften imaged with USI while the device is being inserted into thepatient's breast and activated to remove a sample of suspicious breasttissue. As USI is often used to image tissue during follow-up treatment,it may be desirable to have a marker, similar to the radiographicmarkers discussed above, which can be placed in a patient's body at thesite of a surgical procedure and which are visible using USI. Such amarker enables a follow-up procedure to be performed without the needfor traditional radiographic mammography imaging which, as discussedabove, can be subject to inaccuracies as a result of shifting of thelocation wire as well as being tedious and uncomfortable for thepatient.

Placement of a marker or multiple markers at a location within apatient's body requires delivery devices capable of holding markerswithin the device until the device is properly situated within a breastor other body location. Accordingly, devices and methods for retainingmarkers within a marker delivery device while allowing their expulsionfrom the devices at desired intracorporeal locations are desired.

SUMMARY OF THE INVENTION

The invention is generally directed to the delivery of one or moremarkers to an intracorporeal site within a patient's body. A markerdelivery device embodying features of the invention include a deliverytube or cannula having an inner lumen leading to a discharge opening andhaving a releasable plug which is disposed at least in part within theinner lumen and which at least partially occludes the discharge openingin the distal end of the delivery tube.

The releasable plug is configured to occlude or block off the dischargeopening of the delivery cannula or the inner lumen leading thereto toprevent tissue and fluid from entering the inner lumen through thedischarge opening during delivery and to hold in any other markerswithin the inner lumen proximal to the releasable plug during handlingand delivery. In one embodiment having features of the invention, thedelivery device has a releasable plug with a remotely detectable markerelement incorporated therein. Preferably, the marker elementincorporated into the releasable plug is non-magnetic and remotelydetectable by magnetic resonance imaging.

In yet another embodiment having features of the invention, the deliverydevice has a releasable plug and has at least one short term, remotelydetectable marker mass in the inner lumen or at least one fibrous markerin the inner lumen proximal to the releasable plug. Preferably, at leastone short term marker and at least one fibrous marker are disposedwithin the inner lumen of the delivery cannula.

The releasable plug may be secured within the inner lumen by a varietyof means, but it is preferred to press fit the plug into the distalportion of the inner lumen so as to occlude the discharge opening.However, the plug may alternatively be mechanically or adhesivelysecured within the distal portion of the inner lumen. For further plugdetails see application Ser. No. 10/174,401, filed on Jun. 17, 2002, nowU.S. Pat. No. 7,651,505, entitled Plugged Tip Delivery Tube For MarkerPlacement which is incorporated herein in its entirety by reference.However, the releasable plug should be configured to be easily pushedout of the discharge opening of the delivery cannula, even if thereleasable plug has swollen due to contact with a water based fluid. Asdescribed above, the releasable plug preferably has a non-magnetic, MRIdetectable element which does not interfere with the subsequent imagingof adjacent tissue. The MRI detectable element is about 0.5 to about 5mm in maximum dimension, preferably about 1 to about 3 mm. Suitablenon-magnetic, MRI detectable materials include titanium, platinum, gold,iridium, tantalum, tungsten, silver, rhodium and the like.

The releasable plug is formed of a biocompatible, preferablybioabsorbable material such as oxidized regenerated cellulose,polyethylene glycol, polylactic acid, polyglycolic acid, polycaproicacid, and copolymers, polymer alloys, polymer blends, and combinationsthereof. Preferable materials are oxidized regenerated cellulose andpolymers of polyethylene glycol with molecular weights of about 5000 toabout 120,000 Daltons. The releasable plug should be formed of a waterswellable material, so that it swells upon contact with water basedfluids (e.g. body fluids) to further occlude or otherwise seal thedischarge opening of the delivery cannula and thereby prevent prematurecontact of body fluids with any markers within the inner lumen proximalto the releasable plug. The plug may also be formed of fibrous materialsand be in the form of a fibrous marker described below.

The short term markers disposed within the inner lumen of the deliverycannula proximal to the releasable plug should be remotely detectablefor at least two weeks, preferably at least up to six weeks, but notlonger than about one year, preferably not more than about six months,so as to not interfere with subsequent imaging of the target site. Theshort term markers are preferably formed of bioabsorbable polymericmaterials such as polymers of lactic acid, glycolic acid andcaprolactones and copolymers and blends thereof. Other suitablematerials include those described in application Ser. No. 09/717,909,filed Nov. 20, 2000, now U.S. Pat. No. 6,725,803 and application Ser.No. 10/124,757, filed on Jun. 17, 2002, now U.S. Pat. No. 6,862,470,both of which are incorporated by reference in their entireties. Theplug and the short term markers may be formed of the same or similarmaterial. The releasable plug may also be formed of fibrous material andbe in the form of the fibrous markers described below.

The fibrous marker should be slidably disposed within the inner lumen ofthe delivery cannula, preferably proximal to at least one short termmarker so that upon discharge from the cannula into a target site, thefibrous marker will block the accessing passageway and prevent loss ofmarker material therethrough. A suitable material for forming thefibrous marker is a felt and/or fiber material formed of oxidizedregenerated cellulose which has an in vivo lifetime of a few hours up toabout 6 weeks, typically about 3 days to about 4 weeks. However, thefibrous marker may be formed of a bioabsorbable polymer such aspolylactic acid or polyglycolic acid, a co-polymer of polylactic acidand polyglycolic acid, polycaprolactone, collagen and mixtures thereof,including mixtures with oxidized regenerated cellulose. Suitableoxidized, regenerated cellulose includes SURGICEL™ from the EthiconDivision of Johnson & Johnson or other suitable oxidized regeneratedcellulose which are naturally hemostatic. Alternatively, a hemostaticagent such as collagen, gelatin or polysaccharides may be incorporatedinto the fibrous material to provide the hemostasis upon contact withblood. A wide variety of other hemostatic agents may be incorporatedinto the marker. The thrombus formed by the hemostasis is formed veryquickly to fill the cavity at the biopsy site and at least temporarilyhold the plug and any other markers in position within the cavity.Anesthetic agents to control post procedure pain, chemotherapeuticagents to kill any residual neoplastic tissue and coloring agents (e.g.carbon black and methylene blue) for visual location of the biopsy site,may also be incorporated into the fibrous marker.

The fibrous material is formed into an elongated member, e.g. by rollingor folding, and bound in a compressed condition to provide sufficientcolumn strength to facilitate introduction into and discharge from atubular delivery device. Suitable binding agents for holding the fibrousmarker in a compressed condition are water soluble polymers such aspolyvinyl alcohol, polyethylene glycol, polyvinyl pyrollidone. One ormore radiographically detectable marker elements are provided with atleast one of the fibrous markers, preferably centrally located on theelongated marker to ensure that the radiographically detectable elementis disposed at a more or less central location within the target siterather than at a site margin.

The releasable plug, the short term markers and the fibrous markers mayinclude a variety of therapeutic or diagnostic materials such ashemostatic agents, anesthetic agents, coloring agents, antibiotics,antifungal agents, antiviral agents, chemotherapeutic agents,radioactive agents and the like.

The delivery device preferably has a plunger slidably disposed withinthe inner lumen of the delivery cannula which is movable from an initialposition accommodating the releasable plug and any markers proximal tothe plug within the tube, to a delivery position to push the plug andany desired number of markers out of the discharge opening in the distalend of the cannula into the target tissue site.

Upon being discharged into the intracorporeal target site, the markersat least partially fill the site to enable short term detection byremote imaging and preferably long term detection by remote imagingwithout interfering with imaging of tissue adjacent to the site. Themarkers may swell on contact with body fluid, e.g. blood so as tofurther fill the biopsy cavity. The fibrous marker partially fills thecavity at the target site, positioning the radiopaque marker elementwithin the interior of the target cavity.

The marker mass proximal to the releasable plug may be in the form ofultrasound-detectable, bio-resorbable finely-divided particulatematerial (such as a powder or granulated material), in which many of theparticles have internal cavities. Such particulate materials preferablyhave particle sizes less than about 2000 microns, and typically betweenabout 20 microns and about 2000 microns. For optimum delivery and markerresolution, the particulate should have a particulate size of about 20microns to about 1500 microns, preferably about 500 microns to about 800microns. The ultrasound-detectable, bio-resorbable particulate materialsmay be formed of polymeric materials such as polylactic acid,polyglycolic acid, polycaprolactone, and combinations of these polymersand the particulate may be bound by suitable binding agents such asgelatin, polyethylene glycol, polyvinyl alcohol, glycerin,polysaccharides, other hydrophilic materials, and combinations of these.Suitable gelatins include bovine collagen, porcine collagen, ovinecollagen, equine collagen, synthetic collagen, agar, synthetic gelatin,and combinations of these. Further details of the particulate markermaterial and the delivery thereof can be found in application Ser. No.10/124,757, now U.S. Pat. No. 6,862,470, which has been incorporated byreference herein. Polysaccharide particulate or powder may be includedwith the other particulate materials as a hemostatic agent.

The delivery tube of the device may be configured to fit within a guidecannula, such as a Mammotome® or SenoCor 360™ biopsy cannula or acoaxial needle guide.

The ultrasound-detectable biopsy site markers of the present inventionprovide several advantages. A biopsy cavity with marker material havingfeatures of the present invention provides a large USI-bright mass,making it much easier, for example, to distinguish the ultrasound signalof the marker from signals arising naturally from within a breast. Themarker materials produce bright ultrasound echo signals from one portionof the filled region, which contrasts with the dark ultrasound shadowregion immediately behind the bright ultrasound echo region. Thestrength of the reflected signal, and the contrast with the shadowregion, make the marked site readily detectable. Such readydetectability allows, for example, less-experienced physicians toperform the identification by USI and the subsequent surgical resectionwithout the need for an interventional radiologist to identify and markthe biopsy cavity. When a MRI marker element is incorporated into thereleasable plug or the short term markers, the target site in which themarkers are deployed may be subsequently detected by ultrasound,magnetic resonance and X-ray without interfering with imaging adjacenttissue at a later date.

The invention provides the advantages of securely retaining markerswithin a marker delivery device, improving accuracy and avoiding errorsin placement of markers at desired locations within a patient's body,preventing ingress of tissue into the distal tip of the device when itis advanced through tissue, and guiding the device by use of an imagingdevice including ultrasound, X-ray and magnetic resonance based devices.These and other advantages of the invention will become more apparentfrom the following description when taken in conjunction with theaccompanying drawings.

The invention, in one form thereof, is directed to a marker deliverydevice that includes an elongated delivery cannula which has a distalend section, an inner lumen and a discharge opening in the distal endsection in communication with the inner lumen. At least one elongatedfibrous marker body is slidably disposed within the inner lumen of theelongated delivery cannula. The at least one elongated fibrous markerbody includes a plurality of bioabsorbable polymeric strands. Thestrands are compressed to a compressed configuration and bound togetherin the compressed configuration with a polymer binding agent prior toinsertion into the elongated delivery cannula. A releasable plug isdisposed within a distal portion of the inner lumen and distal to the atleast one elongated fibrous marker body so as to at least partiallyocclude the discharge opening in the distal end section.

The invention, in another form thereof, is directed to a marker deliverydevice for an intracorporeal tissue site. The marker delivery deviceincludes an elongated delivery cannula which has a distal end section, adischarge opening in the distal end section and an inner lumen extendingto and in communication with the discharge opening. A releasable plughas an MRI detectable marker element incorporated therein and isdisposed at least in part within a distal portion of the inner lumen soas to partially occlude the discharge opening in the distal end section.A plurality of elongated fibrous marker bodies is slidably disposedwithin the inner lumen of the elongated delivery cannula proximal to thereleasable plug. Each of the plurality of elongated fibrous markerbodies has a length comprising a plurality of separate bioabsorbablefibers which are compressed and bound together with a synthetic polymerbinding agent so as to form the length prior to insertion into theelongated delivery cannula. A plunger is slidably disposed within theinner lumen of the elongated delivery cannula with a pusher end proximalto the plurality of elongated fibrous marker bodies in the inner lumen.

The invention in another form thereof is directed to a marker deliverydevice for an intracorporeal site within a patient. The marker deviceincludes an elongated delivery cannula which has a distal end, adischarge opening in the distal end and an inner lumen extending to andin communication with the discharge opening. A releasable plug isdisposed within the inner lumen which partially occludes the dischargeopening. At least one short term marker is disposed within the innerlumen proximal to the releasable plug. A plurality of elongated fibrousmarkers are inserted into and slidably disposed within the inner lumenproximal to the at least one short term marker. Each of the fibrousmarkers has a length comprising a plurality of separate bioabsorbablefibers that are compressed and bound together with a polymer bindingagent prior to insertion into the inner lumen of the elongated deliverycannula.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned and other features and advantages of this invention,and the manner of attaining them, will become more apparent and theinvention will be better understood by reference to the followingdescription of an embodiment of the invention taken in conjunction withthe accompanying drawings, wherein:

FIG. 1A is a partly cut-away perspective view of a marker deliveryassembly embodying features of the invention.

FIG. 1B is a transverse cross-sectional view of the marker deliveryassembly of FIG. 1A taken at line 1B-1B.

FIG. 1C is a transverse cross-sectional view of the marker deliveryassembly of FIG. 1A taken at line 1C-1C.

FIG. 2 is an end perspective view of a fibrous marker with a core membersuitable for use with a marker delivery system embodying features of theinvention.

FIG. 3 is an end perspective view of an alternative fibrous markerwithout a core member suitable for use with a marker delivery systemembodying features of the invention.

FIG. 4A-4F illustrates forming a fibrous marker with a core member asdepicted in FIG. 4.

FIG. 5 is a partially cut away, perspective view of a human breast fromwhich a biopsy specimen has been removed, showing a markers beingdelivered to the biopsy site with the marker delivery assembly shown inFIG. 1A.

FIG. 6 is a partial cut-away view of a human breast shown in FIG. 2 withthe markers delivered into the biopsy site and the delivery deviceremoved.

FIG. 7 is a longitudinal cross-sectional view of the distal portion ofan alternative marker delivery device embodying features of theinvention with a sharp, tissue penetrating distal tip.

FIG. 8 is a longitudinal cross-sectional view of the distal portion of amarker delivery device embodying features of the invention havingparticulate marker mass proximal to the releasable plug.

Corresponding reference characters indicate corresponding partsthroughout the several views. The exemplifications set out herein atleast one embodiment of the invention, and such exemplifications are notto be construed as limiting the scope of the invention in any manner.

DETAILED DESCRIPTION OF THE INVENTION

FIGS. 1A-1C illustrate a marker delivery device 10 embodying features ofthe invention which includes a delivery tube or cannula 11 with a bore12, a distal portion 13, and a proximal portion 14 with a handle 15. Areleasable distal plug 16, several (five) short term markers 17, a pairof fibrous markers 18 and 19 and a proximal plug 20 are shown disposedwithin the bore 12. A plunger 21 is slidably disposed within the tubebore 12, and is provided with a proximal end 22 configured to allow anoperator to press the plunger further into the bore 12 and push thereleasable plug 16 and one or more of the other markers out of thedischarge port or opening 23 in the distal end 24 of delivery tube 11.Cannula handle 15 allows an operator to hold the cannula steady whilepressing plunger 21 to discharge the releasable plug 16 and markers 17and 18.

Releasable plug 16 may substantially fill the discharge opening 23, asshown in FIG. 1, or may occupy or block only a portion of the dischargeopening 23. The exposed face of plug 16 is preferably provided with aninclined configuration to conform with the inclination of the dischargeopening 23.

Markers 17, 18 and 19 and proximal plug 20 are preferably configured toslide readily within tube bore 12. Releasable plug 16 is configured tobe tight enough, e.g. press fit, in the bore 12 to prevent itsinadvertent release which would allow premature discharge of markers 17,18 and 19 from delivery tube 11 and undesirable contact with body fluid.But the plug 16 must be easily released when the plunger 21 is presseddeeper into the bore 12 of the delivery tube 11. An adhesive ormechanical element(s) may be used to hold the releasable plug 16 in aposition within the bore 12 to occlude the discharge opening 23.Suitable adhesives include polyurethane or polyacrylic based adhesives,polyhydroxymethacrylate base adhesives, fibrin glue (e.g., Tisseal™),collagen adhesive, or mixtures thereof. Suitable mechanical means forsecuring the releasable plug 16 are described in application Ser. No.10/174,401, now U.S. Pat. No. 7,651,505, which has been incorporatedherein. The distal end 24 of the delivery cannula 11 is provided with aramp 25 which guides the discharged plug 16 and markers 17, 18 and 19out of the side port 26 into the target site. The distal tip 27 may betapered for delivery through a guide tube as shown.

The delivery tube 11 may be provided with markings 28 which serve asvisual landmarks to aid an operator in accurately placing the distal end24 of the cannula 11 in a desired location within a patient's body fordischarging the markers. The markings 37 also be radiopaque,ultrasound-reflective, or otherwise configured to be detectable byremote imaging devices and imaging methods.

Short term markers 17 are made at least in part with detectable,biocompatible materials. Suitable marker materials include bioresorbablepolymeric materials such as poly(esters), poly(hydroxy acids),poly(lactones), poly(amides), poly(ester-amides), poly(amino acids),poly(anhydrides), poly(ortho-esters), poly(carbonates),poly(phosphazines), poly(thioesters), poly(urethanes), poly(esterurethanes), polysaccharides, polylactic acid, polyglycolic acid,polycaproic acid, polybutyric acid, polyvaleric acid, and copolymers,polymer alloys, polymer blends, and combinations thereof. Preferablepolymeric materials are polymers of lactic acid, glycolic acid andcaprolactones. The short term markers 17 may also be formed at least inpart of gelatin. One or more of the short term markers 17 may include aremotely detectable preferably radiopaque element 28.

Releasable plug 16 is preferably formed at least in part of oxidizedregenerated cellulose or polyethylene glycol, but may be made from thesame or similar bioabsorbable materials as marker 17. The polyethyleneglycol quickly expands when contacting a water based fluid such asblood, which ensures that the releasable plug seals off the dischargeopening to prevent premature contact between body fluid (or other waterbased fluid) and the markers 17, 18 and 19 within the bore 12. Thepolyethylene glycol should have a molecular weight of about 5000 toabout 20000 Daltons, preferably about 8000 to about 10000 Daltons in thefinal plug form. The releasable plug 16 preferably has a non-magneticelement 29 incorporated within the body of the releasable plug that isremotely detectable by magnetic resonance imaging (MRI). It may beformed of titanium, platinum, gold, iridium, tantalum, tungsten, silver,rhodium and the like. The MRI detectable element 29 should have amaximum dimension of about 0.5 to about 5 mm, preferably about 1 toabout 3 mm to be MRI detectable. Elements with dimensions greater thanabout 5 mm tend to interfere with the imaging of adjacent tissue.

Releasable plug 16, markers 17, 18 and 19, and plug 20 are configuredfor a slidable fit within the bore 12 of the delivery tube 11. Theexterior of the delivery tube 11 is preferably configured to fit withina guide cannula sized to accept a Mammotome®, Tru-Cut®, or SenoCor®biopsy device. Typically, plug 16 and markers 17 and 18 will havediameters determined by the size of the bore 12 and typically will beabout 0.02 inch (0.5 mm) to about 0.5 inch (12 mm), preferably about0.04 inch (1 mm) to about 0.3 inch (8 mm). Plug 16 may have slightlylarger transverse dimensions to provide a tight fit. In addition, plugs16 and 20 and short term markers 17 will have a length of about 0.04inch (1 mm) to about 0.8 inch (20 mm), preferably about 0.1 inch (2.5mm) to about 0.6 inch (15 mm).

The fibrous markers 18 and 19 are preferably rolled or folded pieces offibrous material such as oxidized cellulose or oxidized, regeneratedcellulose which has been compressed and impregnated with a binding agentsuch as polyethylene glycol and freeze dried in the compressedcondition. The fibrous material may be rolled up by itself, as shown inFIG. 3, or wrapped about a matt-like core 30 as shown in FIG. 2. Thefibrous marker is generally configured to be slidably disposed withinthe inner lumen of the delivery cannula 11, and before delivery is about0.5 mm to about 12 mm, preferably about 1 to about 8 mm in diameter andabout 5 to about 30 mm, preferably about 10 to about 25 mm in length.Upon contact with a body fluid or other water based fluid, the length ofthe fibrous marker remains about the same but the wrapped structureunfolds upon swelling to a width of about 5 to about 25 mm, usuallyabout 10 to about 20 mm. With a radiopaque marker element clamped abouta center portion of the wrapped fibrous marker, the fibrous markerexpands into a generally bow-tie shape when exposed to body fluids.However, even though secured to the fibrous marker, the radiopaquemarker element need not restrict the expansion of the fibrous marker.

The manufacture and use of fibrous marker 18 with a core 30 isschematically illustrated in FIGS. 4A-4F. A felt pad or mat 31 ofoxidized, regenerated cellulose about 0.125 to about 0.375 inch (3.2-9.3mm), preferably about 0.25 inch (6.4 mm) thick is impregnated with a 10%(Wt.) polyethylene glycol in a 70% isopropyl alcohol solution and thencompressed to a mat about 0.03 to about 0.05 inch (0.76-1.3 mm) thick. Areduction in thickness of 80% or more is suitable. The compressed mat 31is cut up into elongated strips 32 with square or near square transversecross-sectional shapes which form the core 30. The core 30 is wrapped ina fabric 33 (i.e., jacket) of oxidized regenerated cellulose about 5 toabout 10 mm in width and about 20 mm in length, compressed andimpregnated with the 10% PEG dispersion and then freeze dried to adiameter of about 0.065 inch (1.65 mm). Elevated temperatures may beemployed to dry the material. The fabric 33 should make at least one,preferably two or more complete wraps about the core 30. The wrapped andcompressed product may then be cut to a desired length to form thefibrous marker 18. Alternatively, the uncompressed mat 31, the strip 32and fiber wrap 33 may be provided at the desired length for the fibrousmarker 18, wrapped and then compressed. A radiographically detectablemarker element 34 may be formed of a radiopaque wire about 0.005 toabout 0.01 inch, (0.13-0.25 mm) may then be crimped about or embedded ina central portion (or other desired portion) of the marker 18. Thefibrous marker 18 is then ready for deployment. As shown in FIG. 1A,only fibrous marker 18 is provided with marker element 34. Marker 19 maybe formed in the same or similar manner but without the radiopaqueelement 34.

Fibrous markers without the core member 30 may be formed by rolling orfolding into the desired configuration. The fibrous material, oxidizedrayon felt is first impregnated with a 10% PEG dispersion, compressedand then freeze dried. The dried felt material is rolled againcompressed in the rolled state, impregnated with a 10-30% PEG solution,and freeze dried in the rolled compressed condition. The rayon feltmaterial can be initially oxidized by treating in a solution of 80% (byvol.) Nitric Acid, 20% (by vol.) Sulfuric Acid and 1% (by weight) SodiumNitrite. The felt is treated in the oxidizing, acidic solution at roomtemperature for about 4.5 hours and then rinsed with deionized water.

Radiopaque elements 28 and 34 may be made with suitable radiopaquematerial, including stainless steel, platinum, gold, iridium, titanium,tantalum, tungsten, silver, rhodium, nickel, bismuth, other radiopaquemetals, alloys and oxides of these metals, barium salts, iodine salts,iodinated materials, and combinations of these. The radiopaque elements28 and 34 may also be configured for detection by MRI. Radiopaquematerials and markers may be permanent, or may be temporary and notdetectable after a period of time subsequent to their placement within apatient. Colorants, such as dyes (e.g., methylene blue and carbon black)and pigments (e.g., barium sulfate), may also be included in markers 17and 19 and plugs 16 and 20 embodying features of the invention.

FIG. 5 schematically illustrates the use of a marker delivery system 10to deliver markers to a desired location 35 within a patient's body. Thedesired location 35 is typically a cavity from which a biopsy sample hasbeen, or is to be, taken, or a lesion that has been or will be removedor otherwise treated. In FIG. 5, the marker delivery system 10 is showninserted into a breast 40 through a guide cannula 41 until the distalend 24 is disposed at the delivery site, cavity 35 where a tissuespecimen has been removed. While an operator holds the system 10 by thehandle 15 of the delivery tube 11, the plunger 21 is pressed furtherinto the bore 12 of delivery cannula 11 to discharge the releasable plug16 and markers 17, 18 and 19 into the cavity 35. FIG. 6 schematicallyillustrates the plug 16 and markers 17, 18 and 19 within the cavity 35after deployment. When the markers contact body fluid within the cavity35, they tend to swell and thereby further fill the cavity. The fibrousmarkers 18 and 19 generally block the accessing track 36 to the cavity35 so that none of the smaller markers 17 will be lost through the track36. Marks 37 are provided on the proximal end of cannula 11 to provideend location information to the operator.

FIG. 7 illustrates the distal portion 50 of cannula 51 of an alternativedelivery system that is essentially the same as that shown in FIGS.1A-1C except that the distal tip 52 of cannula 51 is configured in aneedle-like shape. The delivery system cannula 51 may be used inconjunction with a guide cannula (not shown) or the cannula 51 can beinserted directly through tissue to reach the target site without theneed for a guide cannula. The releasable plug 53 is secured in thedischarge opening 54 as in the previously discussed embodiment. Theexposed face 55 of the plug 53 is preferably flush with the dischargeopening 54 of the distal tip 52.

Insertion of marker delivery devices embodying features of the inventionmay be performed with or without the aid of an imaging device, such asan ultrasound imaging device, an X-ray imaging device, a MRI device, orother imaging device. Alternatively, or additionally, insertion may bevisually guided, or may be guided by palpation or by other means.

The size and composition of the short term markers 17 are selected so asto remain in place within the patient and be detectable by ultrasoundfor at least 2 weeks, preferably at least 6 weeks to have practicalclinical value. However, the short term markers should not be detectableby ultrasound after about one year, preferably not after about sixmonths, so as to avoid interfering with subsequent site examination. Formost clinical purposes, a suitable in-situ lifespan when the short termmarker is ultrasonically detectable is about six to about twenty weeks.The radiopaque and MRI detectable marker elements generally will havemuch longer lifespans.

FIG. 8 illustrates the distal shaft section 60 of an alternativedelivery cannula 61 which has a fibrous releasable plug 62 in the innerlumen 63 of the distal shaft section which at least partially occludesthe discharge opening 64 in the distal end of the shaft. The fibrousreleasable plug 62 may be formed as shown in FIGS. 2, 3 and 4A-F.

The inner lumen proximal to the fibrous releasable plug 62 is filledwith a particulate marker material 65. The corresponding parts of thesystem are the same as that shown in FIGS. 1A-1C. Plunger 66 is slidablydisposed within the inner lumen 63 to eject the powdered mass 65. Theparticulate marker material 65 may be discharged dry or mixed with asuitable fluid and discharged as a slurry.

The particulate may be formed of a biocompatible and bio-resorbablepolymeric material such as polylactic acid, polyglycolic acid,polycaprolactones, poly(esters), poly(hydroxy acids), poly(lactones),poly(amides), poly(ester-amides), poly(amino acids), poly(anhydrides),poly(ortho-esters), poly(carbonates), poly(phosphazines),poly(thioesters), poly(urethanes), poly(ester urethanes),polysaccharides, polybutyric acid, polyvaleric acid, and copolymers,polymer alloys, polymer mixtures, and combinations thereof. Of those,polylactic acid, polyglycolic acid, and polycaproic acid are preferred.The polymeric material in particulate form should have cavities orentrap bubbles which facilitate remote detection.

Suitable particulate materials have particle sizes typically about 20microns to about 2000 microns, preferably about 20 microns to about 800microns and more preferably about 300 microns to about 500 microns. Theparticulate should have cavities for USI with maximum dimensions ofabout 10 microns to about 500 microns, preferably about 20 microns toabout 200 microns. The polymeric particulate materials suitable for usein making ultrasound-detectable biopsy marker materials typically have abulk density of about 0.8 g/ml to about 1.5 g/ml, preferably about 0.8g/ml to about 1 g/ml. The particulate may also contain or be mixed withbinding agents such as polyethylene glycol, polyvinyl alcohol and thelike. Polysaccharide particulate or powder may be incorporated into theparticulate mass in amounts up to about 50% (by weight) of the totalparticulate mass for purposes of hemostasis.

While particular forms of the invention have been illustrated anddescribed herein in the context of a breast biopsy site, it will beapparent that the device and methods having features of the inventionmay find use in a variety of locations and in a variety of applications,in addition to the human breast. Moreover, various modifications can bemade without departing from the spirit and scope of the invention.Accordingly, it is not intended that the invention be limited to thespecific embodiments illustrated. It is therefore intended that thisinvention to be defined by the scope of the appended claims as broadlyas the prior art will permit, and in view of the specification if needbe. Moreover, those skilled in the art will recognize that featuresshown in one embodiment may be utilized in other embodiments. Terms suchas “element”, “member”, “device”, “section”, “portion”, “step”, “means”and words of similar import when used in the following claims shall notbe construed as invoking the provisions of 35 U.S.C. §112(6) unless thefollowing claims expressly use the terms “means” followed by aparticular function without specific structure or “step” followed by aparticular function without specific action. All patents and patentapplications referred to above are hereby incorporated by reference intheir entirety.

This application is intended to cover any variations, uses, oradaptations of the invention using its general principles. Further, thisapplication is intended to cover such departures from the presentdisclosure as come within known or customary practice in the art towhich this invention pertains and which fall within the limits of theappended claims.

1. A marker delivery device for an intracorporeal tissue site,comprising: a) an elongated delivery cannula which has a distal endsection, an inner lumen and a discharge opening in the distal endsection in communication with the inner lumen; b) at least one elongatedfibrous marker body slidably disposed within the inner lumen of theelongated delivery cannula, the at least one elongated fibrous markerbody comprising a plurality of bioabsorbable polymeric strands, saidstrands being compressed to a compressed configuration and boundtogether in the compressed configuration with a polymer binding agentprior to insertion into the elongated delivery cannula; and c) areleasable plug disposed within a distal portion of the inner lumen anddistal to the at least one elongated fibrous marker body so as to atleast partially occlude the discharge opening in the distal end section.2. The marker delivery device of claim 1, wherein the releasable plugcomprises a material that swells in the presence of fluids.
 3. Themarker delivery device of claim 1, wherein the releasable plug comprisesat least one of polyethylene glycol and oxidized cellulose.
 4. Themarker delivery device of claim 3, wherein the polyethylene glycol ofthe releasable plug has a molecular weight of about 5000 to about 20,000Daltons.
 5. The marker delivery device of claim 3, wherein thepolyethylene glycol of the releasable plug has a molecular weight ofabout 8000 to about 10,000 Daltons.
 6. The marker delivery device ofclaim 1, wherein the releasable plug has a non-magnetic marker elementwhich is remotely detectable by magnetic resonance.
 7. The markerdelivery device of claim 1, wherein the releasable plug comprises fibersof bioabsorbable material.
 8. The marker delivery device of claim 7,wherein the fibrous releasable plug has a radiographically detectableelement.
 9. The marker delivery device of claim 8, wherein theradiographically detectable element surrounds an exterior portion of thefibrous releasable plug.
 10. The marker delivery device of claim 9,wherein the bioabsorbable material is selected from the group consistingof polylactic acid, polyglycolic acid, copolymers and blends thereof.11. The marker delivery device of claim 1, comprising a radiographicallydetectable element positioned to surround an exterior portion of arespective fibrous marker body of the at least one elongated fibrousmarker body.
 12. The marker delivery device of claim 1, wherein the atleast one fibrous marker body comprises fibers of oxidized cellulose.13. The marker delivery device of claim 1, wherein the at least onefibrous marker body comprises fibers of oxidized regenerated cellulose.14. The marker delivery device of claim 1, wherein the at least oneelongated fibrous marker body comprises bioabsorbable fibers ofpolymeric material selected from the group consisting of polylacticacids, polyglycolic acids, copolymers and blends thereof.
 15. The markerdelivery device of claim 1, comprising a plunger which is slidablydisposed within the inner lumen of the elongated delivery cannula andwhich has a distal end proximal to the at least one marker body in theinner lumen.
 16. A marker delivery device for an intracorporeal tissuesite, comprising: a) an elongated delivery cannula which has a distalend section, a discharge opening in the distal end section and an innerlumen extending to and in communication with the discharge opening; b) areleasable plug which has an MRI detectable marker element incorporatedtherein and which is disposed at least in part within a distal portionof the inner lumen so as to partially occlude the discharge opening inthe distal end section; c) a plurality of elongated fibrous markerbodies slidably disposed within the inner lumen of the elongateddelivery cannula proximal to the releasable plug, each of the pluralityof elongated fibrous marker bodies having a length comprising aplurality of separate bioabsorbable fibers which are compressed andbound together with a synthetic polymer binding agent so as to form thelength prior to insertion into the elongated delivery cannula; and d) aplunger slidably disposed within the inner lumen of the elongateddelivery cannula with a pusher end proximal to the plurality ofelongated fibrous marker bodies in the inner lumen.
 17. The markerdelivery device of claim 16, wherein the releasable plug expands in thepresence of body fluids.
 18. The marker delivery device of claim 16,wherein the releasable plug comprises a material selected from the groupconsisting of oxidized cellulose, oxidized regenerated cellulose, andpolyethylene glycol.
 19. The marker delivery device of claim 16, whereineach of the plurality of elongated fibrous marker bodies is expandableupon contact with body fluid or other water based fluid.
 20. The markerdelivery device of claim 16, wherein at least one of the plurality ofelongated fibrous marker bodies includes a radiographically detectableelement that surrounds an exterior portion of a respective fibrousmarker body.
 21. The marker delivery device of claim 16, wherein the MRIdetectable marker element is about 0.5 to about 5 mm in maximumtransverse dimension.
 22. The marker delivery device of claim 16,wherein the MRI detectable marker element is about 1 to about 3 mm inmaximum transverse dimension.
 23. A marker delivery device for anintracorporeal site within a patient, comprising: a. an elongateddelivery cannula which has a distal end, a discharge opening in thedistal end and an inner lumen extending to and in communication with thedischarge opening; b. a releasable plug disposed within the inner lumenwhich partially occludes the discharge opening; c. at least one shortterm marker disposed within the inner lumen proximal to the releasableplug; and d. a plurality of elongated fibrous markers which are insertedinto and slidably disposed within the inner lumen proximal to the atleast one short term marker, each of the fibrous markers having a lengthcomprising a plurality of separate bioabsorbable fibers that arecompressed and bound together with a polymer binding agent prior toinsertion into the inner lumen of the elongated delivery cannula. 24.The marker delivery device of claim 23, wherein at least one fibrousmarker of the plurality of elongated fibrous markers has a radiographicimageable element.
 25. The marker delivery device of claim 24, whereinthe radiographically detectable element surrounds a portion of a fibrousmarker of the plurality of elongated fibrous markers.
 26. The markerdelivery device of claim 23, wherein the releasable plug has anon-magnetic, MRI detectable marker element incorporated therein. 27.The marker delivery device of claim 27, wherein the non-magnetic, MRIdetectable marker element is about 0.5 to about 5 mm in maximumdimension.
 28. The marker delivery device of claim 27, wherein thenon-magnetic, MRI detectable marker element is about 1 to about 3 mm inmaximum dimension.
 29. The marker delivery device of claim 23, whereinthe binding agent is a polymer binding agent selected from the groupconsisting of polyvinyl alcohol, polyethylene glycol and polyvinylpyrollidone.
 30. The marker delivery device of claim 23, wherein thereleasable plug is comprised of a material which expands in the presenceof body fluids.